Ketones are ubiquitous chemical entities across the molecular sciences. They serve as versatile intermediates in target-oriented synthesis, are present in a wide range of natural products and drugs, are valuable industrial products and mediate important biochemical pathways. A simple catalytic oxidation of internal alkenes under ambient conditions would therefore represent a powerful synthetic tool to access valuable ketones, since simple internal olefins are easily accessible from petroleum and renewable resources such as seed oils. Additionally, well-established synthetic routes exist to access more functionalized internal alkenes, such as carbonyl olefination and olefin metathesis. Due the lack of an efficient catalytic transformation to synthesize ketones from internal olefins, the hydroboration/oxidation sequence is still commonly used, particularly in target-oriented synthesis. A major drawback of this procedure is the low functional group (“FG”) compatibility of highly reactive borane reagents, as well as the inherent stoichiometric and multistep nature of the process (see, e.g., FIG. 1A). A direct, catalytic methodology to perform this transformation would be highly desirable. A well-studied catalytic transformation to access methyl ketones from terminal olefins is the Tsuji-Wacker reaction, though the success of the transformation is highly substrate-dependent, as shown by the variable reported yields. These aspects considerably limit the scope of the transformation. More recently, Kaneda disclosed an elegant oxygen-coupled, copper-free Wacker oxidation of internal olefins (see, e.g., FIG. 1A). This protocol shows improved substrate scope, but requires the use of high oxygen pressures (initial application of 9 atm pressure followed by 3 atm) and special equipment (autoclave). This limits its application. Therefore, the development of a general and convenient catalyzed oxidation of internal olefins to access ketones is still an unmet challenge in catalysis.
The present invention is directed to solving some of these challenges (FIG. 1B).